Neurofibromin 1 impairs natural killer T-cell-dependent antitumor immunity against a T-cell lymphoma

Jianyun Liu, Richard M. Gallo, Masood A. Khan, Gourapura J. Renukaradhya, Randy R. Brutkiewicz

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Neurofibromin 1 (NF1) is a tumor suppressor gene encoding a Ras GTPase that negatively regulates Ras signaling pathways. Mutations in NF1 are linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. In terms of antitumor immunity, CD1d-dependent natural killer T (NKT) cells play an important role in the innate antitumor immune response. Generally, Type-I NKT cells protect (and Type-II NKT cells impair) host antitumor immunity. We have previously shown that CD1d-mediated antigen presentation to NKT cells is regulated by cell signaling pathways. To study whether a haploinsufficiency in NF1 would affect CD1d-dependent activation of NKT cells, we analyzed the NKT-cell population as well as the functional expression of CD1d in Nf1+/- mice. Nf1+/- mice were found to have similar levels of NKT cells as wildtype (WT) littermates. Interestingly, however, reduced CD1d expression was observed in Nf1+/- mice compared with their WT littermates. When inoculated with a T-cell lymphoma in vivo, Nf1+/- mice survived longer than their WT littermates. Furthermore, blocking CD1d in vivo significantly enhanced antitumor activity in WT, but not in Nf1+/- mice. In contrast, a deficiency in Type-I NKT cells increased antitumor activity in Nf1+/- mice, but not in WT littermates. Therefore, these data suggest that normal NF1 expression impairs CD1d-mediated NKT-cell activation and antitumor activity against a T-cell lymphoma.

Original languageEnglish (US)
Article number1901
JournalFrontiers in immunology
Volume8
Issue numberJAN
DOIs
StatePublished - Jan 5 2018

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Keywords

  • Antitumor immunity
  • CD1d
  • Natural killer T cells
  • Neurofibromin 1
  • T-cell lymphoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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